Neutralizing antibody responses in patients hospitalized with SARS-CoV-2 Delta or Omicron infection
Authors: Susanne L Linderman, Lilin Lai, Estefany L Bocangel Gamarra, Max Sy Lau, Srilatha Edupuganti, Diya Surie, Mark W Tenforde, James D Chappell, Nicholas M Mohr, Kevin W Gibbs, Jay S Steingrub, Matthew C Exline, Nathan I Shapiro, Anne E Frosch, Nida Qadir, Meredith E Davis-Gardner, M Juliana McElrath, Adam S Lauring, Mehul S Suthar, Manish M Patel, Wesley H Self, Rafi Ahmed
Journal: Journal of Clinical Investigation (2022)

To the Editor: Humoral and cellular immune responses contribute to overall protective immunity against SARS-CoV-2, with neutralizing antibody playing a key role in preventing viral infection.This is evident from the large number of Omicron infections occurring in vaccinated and convalescent patients, since antibodies induced after vaccination or infection by the ancestral WA1 strain do not neutralize Omicron variants efficiently (1, 2).These findings have led to the FDA recommendation for inclusion of the Omicron variant in bivalent COVID-19 vaccines.However, issues have been raised about the value of adding Omicron to the vaccine based on data showing only modest differences between antibody responses after booster immunization with Omicron-versus WA1-based vaccines (3,4).Also, a recent study has shown that booster responses to Omicron infection are affected by previous SARS-CoV-2 infections (5).Thus, having additional information on the types of neutralizing antibody responses induced after infection with different SARS-CoV-2 variants will be helpful in addressing this important issue.Here we report live virus neutralization titers against WA1 and the Delta and Omicron (lineages BA.1, BA.2, and BA.5) variants in serum samples collected from hospitalized patients infected with SARS-CoV-2 Delta or Omicron strains.Blood samples were collected from 187 patients hospitalized with acute COVID-19 in the period from July 2021 to March 2022 at 8 US hospitals (Supplemental Methods; supplemental material available online with this article; https://doi.org/10.1172/JCI164303DS1).Of these patients, 26% were immunocompromised (details are shown in Supplemental Table 1).The majority (69%) of the patients were sequence-confirmed for Delta or Omicron infection, and the remaining were classified according to the variant that was dominant at the time of infection.Patients were unvaccinated (n = 80) or vaccinated with COVID-19 mRNA (n = 100) or adenovirus vector (n = 7) vaccine before infection.In unvaccinated Delta-infected patients, the neutralizing antibody response was highly biased toward the infecting Delta strain, with lower titers against WA1 (6-fold) and strikingly lower titers against BA.1 (60-fold) and BA.2 (22-fold) (Figure 1A).In vaccinated Delta-infected patients, neutralization titers against Delta and WA1 were similar, but again were much lower against BA.1 (17-fold) and BA.2 (9-fold) (Figure 1B).Thus, both unvaccinated and vaccinated Delta-infected patients had significantly lower neutralizing antibody responses to Omicron (as determined by Wilcoxon's rank sum test).A strikingly different pattern was seen in Omicron-infected patients irrespective of their vaccination history, with a more favorable